Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 14, 2016, Pages E2047-E2056

  Zhang, Chuanzhao ^a,b   Samanta, Debangshu ^a   Lu, Haiquan ^a   Bullen, John W ^a   Zhang, Huimin ^a   Chen, Ivan ^a   He, Xiaoshun ^b   Semenza, Gregg L ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b SUN YAT SEN UNIVERSITY   (China)

Author keywords

Hypoxia inducible factors; Metastasis; Pluripotency factors; Self renewal; Tumorigenesis

Indexed keywords

6 N METHYLADENOSINE; ALKBH5 PROTEIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; LUCIFERASE; MESSENGER RNA; PROGESTERONE RECEPTOR; PROTEIN; TRANSCRIPTION FACTOR NANOG; UNCLASSIFIED DRUG; ALKBH5 PROTEIN, HUMAN; ALKYLATED DNA REPAIR PROTEIN ALKB HOMOLOG 5; BASIC HELIX LOOP HELIX TRANSCRIPTION FACTOR; ENDOTHELIAL PAS DOMAIN-CONTAINING PROTEIN 1; NANOG PROTEIN, HUMAN;

3' UNTRANSLATED REGION; ARTICLE; BREAST CANCER; CANCER CELL; CONTROLLED STUDY; DEMETHYLATION; HUMAN; HUMAN CELL; HYPOXIA; METHYLATION; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REPORTER GENE; STEM CELL; TUMOR MICROENVIRONMENT; BREAST TUMOR; CANCER STEM CELL; CATALYSIS; CELL HYPOXIA; FEMALE; GENE SILENCING; GENETICS; METABOLISM; PATHOLOGY; PHYSIOLOGY; TUMOR CELL LINE;

ALKB HOMOLOG 5, RNA DEMETHYLASE; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; BREAST NEOPLASMS; CATALYSIS; CELL HYPOXIA; CELL LINE, TUMOR; FEMALE; GENE KNOCKDOWN TECHNIQUES; HUMANS; METHYLATION; NANOG HOMEOBOX PROTEIN; NEOPLASTIC STEM CELLS; RNA, MESSENGER;

EID: 84962632914     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1602883113     Document Type: Article

References (47)

1. DeSantis C, Siegel R, Bandi P, Jemal A (2011) Breast cancer statistics, 2011. CA Cancer J Clin 61(6):409-418.
2. DeSantis CE, et al. (2015) International variation in female breast cancer incidence and mortality rates. Cancer Epidemiol Biomarkers Prev 24(10):1495-1506.
3. O'Shaughnessy J (2005) Extending survival with chemotherapy in metastatic breast cancer. Oncologist 10(suppl 3):20-29.
4. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100(7): 3983-3988.
5. Charafe-Jauffret E, et al. (2009) Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res 69(4): 1302-1313.
6. Oskarsson T, Batlle E, Massagué J (2014) Metastatic stem cells: Sources, niches, and vital pathways. Cell Stem Cell 14(3):306-321.
7. Boyer LA, et al. (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122(6):947-956.
8. Ben-Porath I, et al. (2008) An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40(5):499-507.
9. Hu T, et al. (2008) Octamer 4 small interfering RNA results in cancer stem cell-like cell apoptosis. Cancer Res 68(16):6533-6540.
10. Yu F, et al. (2011) Kruppel-like factor 4 (KLF4) is required for maintenance of breast cancer stem cells and for cell migration and invasion. Oncogene 30(18):2161-2172.
11. Leis O, et al. (2012) Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene 31(11):1354-1365.
12. IV Santaliz-Ruiz LE, Xie X, Old M, Teknos TN, Pan Q (2014) Emerging role of nanog in tumorigenesis and cancer stem cells. Int J Cancer 135(12):2741-2748.
13. 2 histography. Antioxid Redox Signal 9(8):1221-1235.
14. Semenza GL (2012) Hypoxia-inducible factors in physiology and medicine. Cell 148(3): 399-408.
15. Semenza GL (2016) The hypoxic tumor microenvironment: A driving force for breast cancer progression. Biochim Biophys Acta 1863(3):382-391.
16. Regan Anderson TM, et al. (2013) Breast tumor kinase (Brk/PTK6) is a mediator of hypoxia-associated breast cancer progression. Cancer Res 73(18):5810-5820.
17. Mathieu J, et al. (2011) HIF induces human embryonic stem cell markers in cancer cells. Cancer Res 71(13):4640-4652.
18. Conley SJ, et al. (2012) Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia. Proc Natl Acad Sci USA 109(8):2784-2789.
19. Iriondo O, et al. (2015) Distinct breast cancer stem/progenitor cell populations require either HIF1α or loss of PHD3 to expand under hypoxic conditions. Oncotarget 6(31): 31721-31739.
20. Zhang H, et al. (2015) HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells. Proc Natl Acad Sci USA 112(45):E6215-E6223.
21. Xiang L, et al. (2014) Hypoxia-inducible factor 1 mediates TAZ expression and nuclear localization to induce the breast cancer stem cell phenotype. Oncotarget 5(24): 12509-12527.
22. Samanta D, Gilkes DM, Chaturvedi P, Xiang L, Semenza GL (2014) Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells. Proc Natl Acad Sci USA 111(50):E5429-E5438.
23. Lu H, et al. (2015) Chemotherapy triggers HIF-1-dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype. Proc Natl Acad Sci USA 112(33):E4600-E4609.
24. Yoo YG, Christensen J, Gu J, Huang LE (2011) HIF-1α mediates tumor hypoxia to confer a perpetual mesenchymal phenotype for malignant progression. Sci Signal 4(178):pt4.
25. Scheel C, et al. (2011) Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell 145(6):926-940.
26. Schwab LP, et al. (2012) Hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer. Breast Cancer Res 14(1):R6.
27. 6A RNA methylation. Nat Rev Genet 15(5):293-306.
28. 6A-seq. Nature 485(7397):201-206.
29. 6A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell 15(6):707-719.
30. 6A and U-tail. Cell 158(5):980-987.
31. 6-methyladenosine and gene expression control. Nat Rev Mol Cell Biol 15(5):313-326.
32. 6-methyladenosine marks primary microRNAs for processing. Nature 519(7544):482-485.
33. 6-methyladenosine-dependent regulation of messenger RNA stability. Nature 505(7481):117-120.
34. Geula S, et al. (2015) m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science 347(6225):1002-1006.
35. Zheng G, et al. (2013) ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell 49(1):18-29.
36. Thalhammer A, et al. (2011) Human AlkB homologue 5 is a nuclear 2-oxoglutarate dependent oxygenase and a direct target of hypoxia-inducible factor 1α (HIF-1α). PLoS One 6(1):e16210.
37. Neve RM, et al. (2006) A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 10(6):515-527.
38. Zhang H, et al. (2012) HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs. Oncogene 31(14):1757-1770.
39. Dontu G, et al. (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17(10):1253-1270.
40. Ginestier C, et al. (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555-567.
41. Nagata T, et al. (2014) Prognostic significance of NANOG and KLF4 for breast cancer. Breast Cancer 21(1):96-101.
42. Forristal CE, Wright KL, Hanley NA, Oreffo ROC, Houghton FD (2010) Hypoxia inducible factors regulate pluripotency and proliferation in human embryonic stem cells cultured at reduced oxygen tensions. Reproduction 139(1):85-97.
43. Luo W, Chang R, Zhong J, Pandey A, Semenza GL (2012) Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression. Proc Natl Acad Sci USA 109(49):E3367-E3376.
44. Wu MZ, et al. (2015) Hypoxia drives breast tumor malignancy through a TET-TNFα- p38-MAPK signaling axis. Cancer Res 75(18):3912-3924.
45. Pollard PJ, et al. (2008) Regulation of Jumonji-domain-containing histone demethylases by hypoxia-inducible factor (HIF)-1α. Biochem J 416(3):387-394.
46. Mariani CJ, et al. (2014) TET1-mediated hydroxymethylation facilitates hypoxic gene induction in neuroblastoma. Cell Reports 7(5):1343-1352.
47. 6A-seq based on immunocapturing and massively parallel sequencing. Nat Protoc 8(1):176-189.